title: In vitro protection of 3-nitropropionic acid-induced toxicity of astrocytes by basic fibroblast growth factor and thrombin.
abstract: The protective action of basic fibroblast growth factor (bFGF) and thrombin on cultured cortical astrocytes in vitro to the toxic effects of 3-nitropropionic acid (3-NPA) was examined. 3-NPA produced concentration- and time-dependent astrocyte loss as indicated by decrease in the number of glial fibrillary acidic protein (GFAP) positive cells and increase in lactate dehydrogenase (LDH) level of the culture medium. The 3-NPA-induced cellular loss was apparent within 12 h and was maximal at 24 h. The presence of bFGF (10 ng/ml) by itself increased the number of astrocytes at various time intervals, and attenuated the 3-NPA-induced cell loss significantly at various concentrations (0.017-1.7 mM), in 24 and 48 h of exposure. Lower concentrations of thrombin (up to 1 nM) had no effect on the number of astrocytes but higher concentrations (10-100 nM) produced greater cell loss. Thrombin (1 nM) prevented the 3-NPA-induced decrease in GFAP positive cells at both 24 and 48 h intervals. This was further substantiated by the fact that thrombin as low as 0.01 nM attenuated the 3-NPA-induced increase of LDH activity at 24 and 48 h exposure times. But, with 1 nM of thrombin, the attenuation of the LDH activity was seen only at 24 h. The results indicate that 3-NPA produced acute astrocyte toxicity and was attenuated by bFGF and lower concentrations of thrombin.
authors.affiliation: Department of Physiology, Nagoya City University Medical School, Kawasumi 1, Mizuho-Cho, Mizuho-ku, Nagoya 467, Japan.
authors.forename: S B
authors.initials: SB
authors.lastname: Deshpande
authors.forename: H
authors.initials: H
authors.lastname: Nishino
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D016222:Fibroblast Growth Factor 2; D007770:L-Lactate Dehydrogenase; D013917:Thrombin; C015392:3-nitropropionic acid